Blow molded composite devices and method

ABSTRACT

The present disclosure is directed toward a composite balloon comprising a layer of material having a porous microstructure (e.g., ePTFE or expanded polyethylene) and a thermoplastic polymeric layer useful for medical applications. The layers of the composite balloons become adhered through a stretch blow-molding process. Methods of making and using such composite balloons are also described amongst others.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.16/888,978, filed Jun. 1, 2020, which is a continuation of U.S. patentapplication Ser. No. 14/882,330, filed Oct. 13, 2015, now U.S. Pat. No.10,668,257, granted Jun. 2, 2020, which claims the benefit of U.S.Provisional Application 62/064,832, filed Oct. 16, 2014, all of whichare incorporated herein by reference in their entireties for allpurposes.

FIELD OF THE INVENTION

The present disclosure generally relates to composite materials andmethods of making the composite materials or medical device comprisingthe composite materials. The described composite materials can comprisea porous layer adhered to a blow moldable polymer, such as a compositematerial that comprises an expanded fluoropolymer layer that is adheredto a blow moldable polymer through a stretch blow molding process. Inparticular, the precursors for the composite material can be subject toa stretch blow molding process to form the composite material with aballoon shape for medical balloon catheter devices.

BACKGROUND

Medical balloons are useful for many endovascular treatments includingdilatation of a body vessel, and drug delivery, and expansion andseating of a medical device such as a stent. Medical balloons may bemade of a single layer of material or of multiple layers of material. Inthe case of multi-layer or composite balloons, the multiple layerswithin the composite may be different materials to obtain a blend ofphysical or chemical properties to optimize performance in someparticular way(s), depending on the application.

Expanded polytetrafluoroethylene (ePTFE) is of interest for use inmedical balloons because of its low coefficient of friction, chemicalresistance, porous microstructure, flexibility, and strength. Because ofthe physical properties of ePTFE, however, the material cannot beprocessed in the same way that conventional thermoplastic elastomers areprocessed. In particular, adhering ePTFE to other materials is difficultbecause it has a low surface energy and a very high melt viscosity. Newcomposite materials with ePTFE and ways of making said composites can bebeneficial.

SUMMARY

The present disclosure is directed to composite balloons comprising aporous polymer layer such as ePTFE adhered to a blow moldable polymericlayer and a stretch-blow molding process to form such compositeballoons.

In one aspect of the disclosure, a composite medical balloon isdescribed. Some composite medical balloon embodiments can comprise aballoon wall defining a chamber and comprising a layered material,wherein the layered material comprises a polyamide layer at leastpartially adhered to a polymeric layer comprising a porousmicrostructure, wherein the porous polymeric layer is an outermostlayer. Others can comprise a balloon wall defining a chamber andcomprising a layered material, wherein the layered material comprises aseamless polymeric layer at least partially adhered to a polymeric layercomprising a porous microstructure, wherein the porous polymeric layeris an outermost layer and wherein the seamless polymeric layer is acompliant, semi-compliant, or non-compliant material. Still others cancomprise a balloon wall defining a chamber and comprising a layeredmaterial, wherein the layered material comprises a first polymeric layerat least partially adhered to a second, anisotropic or isotropicpolymeric layer comprising a porous microstructure. Other balloonembodiments can comprise a balloon wall defining a chamber andcomprising a layered material, wherein the layered material comprises aseamless polymeric layer mechanically adhered to a seamless polymericlayer comprising a porous microstructure, wherein the porous polymericlayer is an outermost layer. In various embodiments, the porouspolymeric layer is an expanded fluoropolymer, such as expandedpolytetrafluoroethylene. The first or seamless polymeric layer is a blowmoldable thermoplastic, such as polyamide. Depending on the selection ofthe material of the first or seamless polymeric layer, the balloon canbe compliant, semi-compliant, or non-compliant. The underlying layer canbe configured to prevent an inflation fluid from passing through theballoon wall.

In a further aspect of the disclosure, a medical balloon can comprise aballoon wall defining a chamber and comprising a layered material thatdefines an outer surface of the medical balloon, wherein the layeredmaterial comprises a polymeric layer having a porous microstructure andwherein the layered material comprises one or more recessed regions orone or more protruding regions on the outer surface. The recessedregions comprise a region of collapsed pores in the porous polymericlayer. In some embodiments, the recessed regions comprise a porouspolymeric layer thickness that is 90% or less relative to the porouspolymeric layer thickness of the non-recessed region. For example, arecessed region can comprise a thickness that is 10%, 15%, 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% ofthe thickness of the non-recessed region. The combination of recessesand protrusions can form a striated pattern, oriented radially orlongitudinally. While some patterns are described, it is to beunderstood that the pattern can be any selected pattern, whether regularor random. In some embodiments, the maximum width of the protrusions canbe between 0.1 mm to 1 mm, such as 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mm or any value therebetween. Invarious embodiments, the balloon surface defines a plurality of recessesand protrusions within the working length and wherein the protrusionscover about 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or any valuetherebetween of the total balloon surface area within the workinglength.

Other aspects of the disclosure are directed to methods of using thedescribed composite balloons in a medical procedure. Such methods cancomprise passing the balloon catheter device with a composite balloonmounted thereon through an anatomical conduit or vessel to the desiredposition and inflating the described balloon to a nominal diameter. Themethod can further comprise expanding a medical device that is disposedabout the balloon or delivering, upon inflation, a therapeutic agentthat is on the outer surface of the balloon to a surrounding tissue orendovascular device.

Still other aspects of the disclosure relate to methods of making thedescribed balloon composites. Various embodiments comprise radiallyexpanding, in a mold, a thermoplastic balloon preform and a polymerictubular member comprising a porous microstructure to form a layeredballoon body, wherein the tubular member is disposed about the balloonpreform and wherein the portions of the tubular member and the balloonpreform within the mold become mechanically adhered while in a radiallyexpanded state. Some embodiments comprise radially expanding, in a mold,a thermoplastic balloon preform and a polymeric tubular membercomprising a porous microstructure, wherein the tubular member isdisposed about the balloon preform and applying heat to the radiallyexpanded balloon preform and the polymeric tubular member at atemperature at or above the glass transition temperature of thethermoplastic balloon preform but below the melt temperature (T_(m)) ofthe thermoplastic balloon preform to form a layered balloon body. Theportions of the outermost polymeric layer and the underlying layerwithin the mold become mechanically adhered while in a radially expandedstate.

In an alternative embodiment, the balloon body may be formed in fullfrom a balloon preform without first adding a polymeric tubular membercomprising a porous microstructure. Some embodiments comprise radiallyexpanding, in a mold, a thermoplastic balloon preform, and applying heatto the radially expanded balloon preform at a temperature at or abovethe glass transition temperature of the thermoplastic balloon preformbut below the melt temperature (T_(m)) of the thermoplastic balloonpreform to form a layered balloon body. The formed balloon body may besubjected to manual or mechanical pleating, folding, and othersubsequent manual or mechanical manipulation prior to the addition of apolymeric tubular member comprising a porous microstructure. Once thepolymeric tubular member comprising a porous microstructure is placedaround a thermoplastic balloon body, a layered balloon body is formed.While the tubular member and balloon body are inflated within a mold,the temperature of the mold can be at or above the glass transitiontemperature (T_(g)) of the thermoplastic balloon body. For example, invarious embodiments, the temperature can be between T_(g) andT_(g)+½(T_(m)−T_(g)); between T_(g) and T_(g)+⅓(T_(m)−T_(g)); or betweenT_(g) and T_(g)+¼(T_(m)−T_(g)). (T_(m) is the melt temperature of thethermoplastic balloon body.) In some embodiments, the temperature of themold can be at or above the glass transition temperature (T_(g)) butbelow the melt temperature of the thermoplastic. In other embodiments,the temperature of the mold can be at or above the melt temperature ofthe thermoplastic. In this manner, the composite structure is formedinto a composite balloon. The portions of the outermost polymeric layerand the underlying layer within the mold become mechanically adheredwhile in a radially expanded state in the formation of a compositeballoon.

In some embodiments, the mold can have an inner surface that defines oneor more recesses and wherein the formed composite balloon body comprisesone or more recessed regions on the outer surface formed by a section ofthe tubular member being forced against a non-recessed section of theinner surface of the mold while in a radially expanded state. Duringradial expansion and heat setting, the temperature of the mold or insidethe mold can be at or above the glass transition temperature (T_(g)) ofthe thermoplastic polymer. In further embodiments, the temperature isbetween the T_(g) and the T_(m) of the thermoplastic polymer. Duringradial expansion and heat setting, the pressure in the mold causingradial expansion (such as with an inflation fluid) can be between 15 barto 40 bar for a mold of 4 to 8 mm in diameter. The pressure can dependon the compliancy of the selected blow moldable, thermoplastic polymer.The polymeric tubular member is a circumferentially or helically wrappedtube of a polymeric film.

Another aspect of the disclosure relates to methods of making thedescribed composite balloons with one or more recesses and/orprotrusions on the outer surface. In some embodiments, the method cancomprise providing a mold having an inner surface that defines one ormore recesses; radially expanding a polymeric tubular member comprisinga porous microstructure in the mold to form a balloon body, wherein theballoon body comprises one or more recessed regions formed by a sectionof the tubular member being forced against a non-recessed section of theinner surface of the mold during expansion. The maximum width of the oneor more recesses in the mold is between 0.1 mm to 1 mm, such as 0.1 mm,0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mmor any value therebetween. The depth of each of the one or more moldrecesses can be about 1.0x, 1.3x, 1.5x, 1.7x, or 2.0x, where x is thewidth of the recess. During radial expansion and heat setting, thetemperature of the mold or inside the mold can be at or above the glasstransition temperature (T_(g)) of the thermoplastic polymer. In furtherembodiments, the temperature is between the T_(g) and the T_(m) of thethermoplastic polymer. In still further embodiments, the temperature ofthe mold or in the mold can be at or above the melt temperature of thethermoplastic. During radial expansion and heat setting, the pressure inthe mold causing radial expansion (such as with an inflation fluid) canbe from 1 bar up to 40 bar for a mold of 4 to 8 mm in diameter. Thepressure can depend on the compliancy of the selected blow moldable,thermoplastic polymer. The polymeric tubular member is acircumferentially or helically wrapped tube of a polymeric film.

Another aspect of the disclosure is a method of applying a therapeuticagent to the described balloons. In some embodiments, the methodcomprises applying one or more therapeutic agents to the balloon priorto mounting on a catheter. In further embodiments, the therapeutic agentis applied to the recesses on the balloon surface. In furtherembodiments, the therapeutic agent is applied to protrusions on theballoon surface. In still further embodiments, the therapeutic agent isapplied to recesses and protrusions on the balloon surface.

Yet another aspect of the disclosure can be an assembly for making amedical balloon comprising a balloon mold defining a chamber; athermoplastic balloon preform or fully formed balloon body; and apolymeric tubular member comprising a porous microstructure, wherein thetubular member is disposed about the balloon preform or the formedballoon body and wherein at least a portion of the tubular member andthe balloon preform or the formed balloon body are disposed within thechamber.

The terms “a” and “an” are defined as one or more unless this disclosureexplicitly requires otherwise.

The terms “substantially,” “approximately” and “about” are defined asbeing largely but not necessarily wholly what is specified (and includewholly what is specified) as understood by one of ordinary skill in theart. In any disclosed embodiment, the term “substantially,”“approximately,” or “about” may be substituted with “within [apercentage] of” what is specified, where the percentage includes 0.1, 1,5, and 10 percent. The term “majorly” indicates at least half.

The terms “comprise” (and any form of comprise, such as “comprises” and“comprising”), “have” (and any form of have, such as “has” and“having”), “include” (and any form of include, such as “includes” and“including”) and “contain” (and any form of contain, such as “contains”and “containing”) are open-ended linking verbs. As a result, any of thepresent devices, systems, and methods that “comprises,” “has,”“includes” or “contains” one or more elements possesses those one ormore elements, but is not limited to possessing only those one or moreelements. Likewise, an element of a device, system, or method that“comprises,” “has,” “includes” or “contains” one or more featurespossesses those one or more features, but is not limited to possessingonly those one or more features.

Any of the present devices, systems, and methods can consist of orconsist essentially of—rather than comprise/include/contain/have—any ofthe described elements and/or features and/or steps. Thus, in any of theclaims, the term “consisting of” or “consisting essentially of” can besubstituted for any of the open-ended linking verbs recited above, inorder to change the scope of a given claim from what it would otherwisebe using the open-ended linking verb.

Furthermore, a structure that is capable of performing a function orthat is configured in a certain way is capable or configured in at leastthat way, but may also be capable or configured in ways that are notlisted.

The preposition “between,” when used to define a range of values (e.g.,between x and y) means that the range includes the end points (e.g., xand y) of the given range and the values between the end points.

As used herein, “nominal diameter” means the approximate diameter of theballoon at the nominal inflation pressure. Beyond this state, pressureincreases (e.g., up to the rated burst pressure) result in less than a20% increase in diameter, less than a 15% increase in diameter, or lessthan a 10% increase in diameter. Typically, the nominal diameter is thelabeled diameter as indicated on the instructions for the end user,e.g., a clinician.

The term “imbibed” or “imbibing” as used herein is meant to describe anystate or mode for majorly or substantially filling a region of pores ofa porous material such as ePTFE or the like but does not refer tofilling the pores with a therapeutic agent or a therapeutic agentcombined with excipients.

As used herein, “angioplasty pressure” means the minimum pressurerequired to perform a Percutaneous Transluminal Angioplasty (PTA)procedure for a balloon of a certain size. This value is dependent onthe size of the balloon, and can be within the working pressure rangebetween the nominal inflation pressure to the rated burst pressure, thenominal inflation pressure being the minimum pressure at which theballoon reaches nominal diameter and rated burst pressure being theupper limit of a pressure range for a medical balloon provided by themanufacturer.

As used herein, “balance ratio” means ratio of machine direction matrixtensile strength to transverse direction matrix tensile strength. Wherethe matrix tensile strengths in the machine and transverse direction arenot substantially equal, a material can be said to be “anisotropic.”Where the matrix tensile strength in the machine and transversedirection are substantially equal, the material can be said to be“isotropic”.

As used herein, a “semi-compliant” balloon is one that has less thanabout 20% diametric growth (e.g., less than a 20% increase in theballoon diameter relative to the nominal diameter) when inflated fromthe nominal inflation pressure to the rated burst pressure. As usedherein, a “non-compliant” balloon is one that has less than about 10%diametric growth when inflated from the nominal inflation pressure tothe rated burst pressure. As used herein, a compliant balloon is onethat has greater than 20% increase in the balloon diameter relative tothe nominal diameter. Such a compliant balloon will conform to the shapeof a vessel lumen.

As used herein, “medical device” means any medical device capable ofbeing implanted and/or deployed within a body lumen or cavity. Invarious embodiments, a medical device can comprise an endovascularmedical device such as a stent, a stent-graft, graft, heart valve, heartvalve frame or pre-stent, occluder, sensor, marker, closure device,filter, embolic protection device, anchor, drug delivery device, cardiacor neurostimulation lead, gastrointestinal sleeves, and the like.

The feature or features of one embodiment may be applied to otherembodiments, even though not described or illustrated, unless expresslyprohibited by this disclosure or the nature of the embodiments.

Details associated with the embodiments described above and others arepresented below.

BRIEF DESCRIPTION OF THE DRAWINGS

The features and advantages of the present disclosure will become moreapparent from the detailed description set forth below when taken inconjunction with the drawings, wherein:

FIG. 1 a illustrates a medical balloon embodiment in accordance with thepresent disclosure.

FIG. 1 b illustrates a cross-section of the composite material formingthe medical balloon embodiment shown in FIG. 1 a.

FIG. 2 is a schematic of a balloon mold with a tubular precursorpositioned about a thermoplastic preform and disposed within the cavityof the mold.

FIG. 3 a illustrates a medical balloon embodiment comprising a reliefpattern on the outer surface in accordance with the present disclosure.

FIG. 3 b illustrates a cross-section of the composite material formingthe medical balloon embodiment shown in FIG. 3 a and showing therecesses and protrusions in the outer surface.

FIG. 4 is a transverse, cross-sectional schematic of the interiorsurface of a balloon mold for forming a series of protrusions andrecesses that create a striped pattern much like that depicted in FIG. 3a.

FIG. 5 a illustrates a medical balloon embodiment in accordance with thepresent disclosure with a coating of a therapeutic agent.

FIG. 5 b illustrates a medical balloon embodiment in accordance with thepresent disclosure with a stent device disposed thereon.

FIGS. 6 a and 6 b are SEM images of the Example 1 film; an image of eachside.

FIG. 6 c is an SEM image of the Example 2 film.

FIG. 7 a is a table of the heat-setting conditions for the balloonbodies made in Example 3.

FIGS. 7 b (i)-(ii) are tables of the results for the Peel Test describedin Example 6.

FIG. 8 a is an SEM image of a patterned balloon showing a recess region312 and a protruding region 314 in the ePTFE microstructure. FIG. 8 b isan SEM image at a higher magnification showing the microstructure at aprotruding region and, conversely, FIG. 8 c is an SEM image at a highermagnification showing the microstructure at a recessed region. FIG. 8 dis an SEM image of the cross-section of the same patterned compositethat shows the relative amounts of microstructure thickness, as aportion of a recess is shown on the left-hand side of the image and theprotruding region is central in the image.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

Persons skilled in the art will readily appreciate that various aspectsof the present disclosure can be realized by any number of methods andapparatuses configured to perform the intended functions. Stateddifferently, other methods and apparatuses can be incorporated herein toperform the intended functions. It should also be noted that theaccompanying drawing figures referred to herein are not all drawn toscale, but may be exaggerated to illustrate various aspects of thepresent disclosure, and in that regard, the drawing figures should notbe construed as limiting. Finally, although the present disclosure maybe described in connection with various principles and beliefs, thepresent disclosure should not be bound by theory.

Surprisingly, the inventors discovered that by stretch blow molding athermoplastic polymeric preform with a porous tubular member (e.g., anePTFE tube) surrounding it, the two separate members become adhered toform a composite balloon member without any adhesive agents or surfacetreatments. Similarly, a fully formed balloon body with a porous tubularmember (e.g., an ePTFE tube) surrounding it can be heated andpressurized to form a composite balloon member without the use of anyadhesive agents or surface treatments. Such blow molded composites canform a medical balloon that exhibits a lubricious outer surface, a lowdiametric profile, and/or rated burst pressures in the range of, e.g., 5bar to 40 bar or more—the value being dependent upon the dimensions ofthe balloon and the properties of the respective layers amongst otherthings, and the orientation of the microstructure. The rated burstpressure and the compliance can be tailored based upon the materialproperties of the respective layers.

With such blow molded composite balloons, the outer layer material actsin a unitary manner with the underlying layer. In comparison, a discretecover over a balloon can move independently of the underlying ballooncausing the cover to gather or deform in certain areas, which can beunpredictable and/or undesired.

Another realized benefit relative to balloons with “floating” ePTFEcovers involves the issue of trapped air. It is not uncommon for air tobecome trapped between the cover and the balloon of such devices, and aprocessing step to remove such trapped air between may be required toensure patient safety. Composite balloons of the present disclosurewould not have this issue as the layers are unitary without the use of aseparate adhesive material or additional surface treatment step.

Accordingly, the present disclosure is directed towards a compositeballoon comprising a layer of material having a porous microstructure(e.g., ePTFE or expanded polyethylene) and a thermoplastic polymericlayer useful for medical applications. As mentioned above, the layers ofthe composite balloons become adhered through a stretch blow moldingprocess. The process conditions involve a temperature that is at orabove the glass transition temperature (T_(g)) of the thermoplasticpolymer. While not wishing to be bound by any particular theory, it isbelieved that the layers within the composite balloons of the presentdisclosure become mechanically adhered through the stretch blow moldingprocess.

During the stretch blow molding process, due to the multi-directionalpressures on the porous microstructure, some types of porousmicrostructure may collapse (and lose some loft), which may be undesiredfor some applications. Thus, to mitigate this effect, a patterned moldcan be utilized that reduces this effect for a portion of the balloon'ssurface area. Accordingly, the present disclosure is also directedtowards a composite balloon comprising an outermost layer of materialhaving a porous microstructure and thermoplastic layer where the outersurface of the balloon comprises a recess (or protrusion) or a pluralityof recesses (or protrusions). The recesses can be selectively formed byusing a mold having a relief (or sunken relief) on its inner surface tocreate areas of more compression of the porous microstructure relativeto protruding areas.

According to the present disclosure, with reference to FIGS. 1 a-1 b , amedical balloon 100 comprises a balloon wall 110 defining a chamber andcomprising a layered material 6, wherein layered material 6 comprises athermoplastic polymeric layer 4 at least partially adhered to apolymeric layer 5 comprising a porous microstructure (referred to hereinas a “porous layer”). As mentioned above, the adhesion is createdthrough a stretch blow molding process. In various embodiments,thermoplastic layer 4 serves as the bladder to retain the inflationfluid and thus is composed of an impermeable or fluid-tight material. Inaddition, in various embodiments, the porous polymeric layer 5 can bethe innermost or outermost layer.

In order to make such balloon body composites by one of the severalmethods described, with reference to FIG. 2 , a polymeric tubular member210 comprising a porous microstructure is placed around a thermoplasticballoon preform (parison) 220 and both are radially expanded in aballoon mold 230 to form a layered balloon body. While tubular member210 and balloon preform (parison) 220 are inflated within balloon mold230, the temperature of the mold can be at or above the glass transitiontemperature (T_(g)) of the thermoplastic balloon preform. For example,in various embodiments, the temperature can be between T_(g) andT_(g)+½(Tm−T_(g)); between T_(g) and T_(g)+⅓(T_(m)−T_(g)); or between Tgand Tg+¼(T_(m)−T_(g)). (T_(m) is the melt temperature of thethermoplastic preform.) In some embodiments, the temperature of the moldcan be at or above the glass transition temperature (T_(g)) but belowthe melt temperature of the thermoplastic. In other embodiments, thetemperature of the mold can be above the melt temperature of thethermoplastic.

In an alternative embodiment, the balloon body 100 is formed in fullwithout first adding a polymeric tubular member comprising a porousmicrostructure. The formed balloon body 100 is subjected to manual ormechanical pleating, folding, and other subsequent manual or mechanicalmanipulation prior to the addition of a polymeric tubular membercomprising a porous microstructure 210. The polymeric tubular membercomprising a porous microstructure 210 is placed around a thermoplasticballoon body 310. When tubular member 210 and balloon body 100 areinflated within mold 230, the temperature of the mold is raised to orabove the glass transition temperature (T_(g)) of the thermoplasticballoon preform. For example, in various embodiments, the temperature isbetween T_(g) and T_(g)+½(T_(m)−T_(g)); between T_(g) andT_(g)+⅓(T_(m)−T_(g)); or between T_(g) and T_(g)+¼(T_(m)−T_(g)). (T_(m)is the melt temperature of the thermoplastic preform.) In someembodiments, the temperature of the mold is at or above the glasstransition temperature (T_(g)) but below the melt temperature of thethermoplastic. In other embodiments, the temperature of the mold isabove the melt temperature of the thermoplastic. In this manner, thecomposite structure is formed into a composite balloon.

Through this process, the portions of tubular member 210 and underlyingthermoplastic preform (parison) 220 within balloon mold 230 become atleast partially adhered. The adhesion created through this process isreferred to herein as “mechanical adhesion.” The mechanical adhesion isnot caused by an adhesive agent (e.g., a glue) or by chemical bonds(covalent or ionic bonds). While not wishing to be bound by anyparticular theory, it is postulated that the mechanical adhesionobserved in the embodiments described herein is caused by a conformingor interlocking of a polymer with the surface irregularities (e.g., aporous microstructure) of the porous polymer. This process results inadhering the two layers 4, 5 (FIG. 1 b .) together.

In various embodiments, the degree of adhesion can be increased byincreasing the temperature during the shape-setting phase of the blowmolding process, which occurs in the later portion of the process. Inaddition, the degree of adhesion can be increased by increasing thepressure during the shape-setting phase of the blow molding process. Thepressure during the shape-setting phase can be up to 40 bar depending onthe materials being used and the intended results of the process. Invarious embodiments, the pressure during the shape-setting phase can be5 bar, 10 bar, 15 bar, 20 bar, 25 bar, 30 bar, 40 bar, 45 bar, 50 bar,60 bar, or any value therebetween. While a pressure range has beenindicated, it is to be understood that pressures can exceed the high endof the stated range because the mold will provide a counter force thatprevents the forming balloon from deforming or bursting. It is also tobe understood that pressures may be lower than those stated, as thepressure needed to cause radial expansion will depend on the strengthand thickness of the materials (balloon preforms or balloon bodies andtubular members) used. Because of the manner in which the balloon bodyis formed, the thermoplastic polymer preform 220 and ultimately thelayer in the composite balloon wall can be seamless.

In accordance with another aspect of the disclosure, a balloon moldingassembly 200, as shown in FIG. 2 , can comprise polymeric tubular member210 comprising a porous microstructure disposed around a thermoplasticballoon preform (parison) 220 and positioned within the chamber ofballoon mold 230.

Preform (parison) 220 can be formed in any variety of polymericprocesses, e.g. an injection molding, a blow molding, or an extrusionprocess. In some embodiments, preform (parison) 220 can bepre-conditioned by stretching in a balloon stretch machine underelevated temperatures before the composite-forming step in order toincrease the reliability of the composite-forming step. In variousembodiments, preform (parison) 220 is stretched at least 1.5×, 2×, 2.5×,or 3× its length.

The thermoplastic layer 4 or preform (parison) 220 can be composed of acompliant, semi-compliant or non-compliant thermoplastic polymer.Suitable thermoplastics include polymers that are medical grade and areblow moldable. In various embodiments, the thermoplastic material canhave a glass transition temperature below 360° C., 325° C., 300° C.,275° C., 250° C., 225° C., 200° C. or any value therebetween. Examplesof suitable thermoplastics can include polymethyl methacrylate (PMMA orAcrylic), polystyrene (PS), acrylonitrile butadiene styrene (ABS),polyvinyl chloride (PVC), modified polyethylene terephthalate glycol(PETG), cellulose acetate butyrate (CAB); semi-crystalline commodityplastics that include polyethylene (PE), high density polyethylene(HDPE), low density polyethylene (LDPE or LLDPE), polypropylene (PP),polymethylpentene (PMP); polycarbonate (PC), polyphenylene oxide (PPO),modified polyphenylene oxide (Mod PPO), polyphenylene ether (PPE),modified polyphenylene ether (Mod PPE), thermoplastic polyurethane(TPU); polyoxymethylene (POM or Acetal), polyethylene terephthalate(PET, Thermoplastic Polyester), polybutylene terephthalate (PBT,Thermoplastic Polyester), polyimide (PI, Imidized Plastic),polyamide-imide (PAI, Imidized Plastic), polybenzimidazole (PBI,Imidized Plastic); polysulfone (PSU), polyetherimide (PEI), polyethersulfone (PES), polyaryl sulfone (PAS); polyphenylene sulfide (PPS),polyether ether ketone (PEEK); fluoropolymers that include fluorinatedethylene propylene (FEP), ethylene chlorotrifluoroethylene (ECTFE),ethylene tetrafluoroethylene (ETFE), polychlorotrifluoroethylene(PCTFE), polyvinylidene fluoride (PVDF), perfluoroalkoxy (PFA), orcombinations, copolymers, or derivatives thereof. Other commonly knownmedical grade materials include elastomeric organosilicon polymers, andpolyether block amide (e.g., PEBAX®). In particular, polyamides caninclude nylon 12, nylon 11, nylon 9, nylon 6/9, and nylon 6/6. Incertain embodiments, PET, nylon, and PE may be selected for medicalballoons used in coronary angioplasty or other high pressureapplications. The specific choice of materials depends on the desiredcharacteristics/intended application of the balloon.

As described above, the porous layer is formed from tubular member 210of a polymer having a porous microstructure. Tubular member 210 can beformed as an extruded tube or can be film-wrapped. Tubular member 210can have circumferential, helical, or axial orientations of themicrostructure. In various embodiments, tubular member 210 can be formedby wrapping a film or tape and the orientation can be controlled by theangle of the wrapping. Tubular member 210 can be circumferentiallywrapped or helically wrapped. When the porous material is wrappedhelically versus circumferentially or axially, the degree of compliancyin a given direction can be varied and can influence the overallcompliancy of the composite. (As used herein, the term “axial” isinterchangeable with the term “longitudinal.” As used herein,“circumferential” means an angle that is substantially perpendicular tothe longitudinal axis.)

The porous tubular member 210 can be isotropic or anisotropic. Invarious embodiments, in the composite material, the anisotropic porouspolymeric layer is oriented such that the balloon wall has a highertensile strength in the longitudinal direction than the radialdirection. In other embodiments, the anisotropic porous polymeric layeris oriented such that the balloon wall has a lower tensile strength inthe longitudinal direction than the radial direction. In variousembodiments, the balance ratio of the material layer can be between 1:1and 70:1, such as 2:1, 5:1, 7:1, 10:1, 12:1, 14:1, 16:1, 18:1, 20:1,22:1, 24:1, 26:1, 28:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1,70:1, or any value or range therebetween. In embodiments where thethermoplastic polymer is a compliant material, the axial modulus and/orlongitudinal modulus, and thus the balance ratio can be tuned to controldistension in the radial and/or longitudinal direction.

The architecture of porous microstructure can be selected based on theneeds of the intended application. In various embodiments, the porousmicrostructure can be substantially fibrillated (e.g., a non-woven webhaving a microstructure of substantially only fibrils, some fused atcrossover points or with smaller nodal dimensions). In otherembodiments, the porous material can comprise large nodes or largedensified regions that may have an impact on the extent ofcompressibility/collapsibility of the material during blow molding. Instill other embodiments, the porous microstructure can be a node andfibril microstructure between these two. In some embodiments, the porousmaterial can have an “open” microstructure such that the outer layer canhave more loft and/or a drug coating can have more void space to occupynear the surface of the layer. The material described in Example 1 is anexample of a material that comprises an open microstructure. Otherexamples of porous architectures can be fibrous structures (such aswoven or braided fabrics), non-woven mats of fibers, microfibers, ornanofibers, flash spun films, electrospun films, and other porous films.

In various embodiments, the porous material can comprise expandedfluoropolymers or expanded polyethylene (see e.g., U.S. Pat. No.6,743,388 (to Sridharan). Non-limiting examples of expandablefluoropolymers include, but are not limited to, ePTFE, expanded modifiedPTFE, and expanded copolymers of PTFE. Patents have been filed onexpandable blends of PTFE, expandable modified PTFE, and expandedcopolymers of PTFE, such as, for example, U.S. Pat. No. 5,708,044 toBranca; U.S. Pat. No. 6,541,589 to Baillie; U.S. Pat. No. 7,531,611 toSabol et al.; U.S. Pat. No. 8,637,144 to Ford; and U.S. Pat. No.8,937,105 to Xu et al.

In various embodiments, the pores of a portion of the porous layer canbe devoid of a polymeric filler material, except for perhaps theinterface between the two layers. In this way, the porous material cancomprise microstructure that is not imbibed with a second polymericmaterial. While some embodiments of the present disclosure are notimbibed, it is to be understood that by increasing the temperatureand/or pressure, deeper penetration into the porous material can becaused.

The degree of adhesion between the layers is measurable by a “Peel Test”as described herein. In various embodiments, the two layers of thecomposite are capable of separating in a 157° Peel Test with a minimumof 1 N/m of average kinetic force. In various embodiments, the averagekinetic force of the Peel Test can be at least 5 N/m, 10 N/m, 15 N/m, 20N/m, 25 N/m, 30 N/m, 35 N/m, 40 N/m or between any range derivabletherefrom. This range can be further expanded up to the tensile limit ofeither layer of composite material, and is dependent upon the nature ofthe materials used. The amount of adhesion can be increased byincreasing the temperature and/or pressure of the blow molding process.

In various embodiments, the rated burst pressure of a balloon can behigher than what the balloon would otherwise be without theincorporation of the porous layer. For example, a composite balloon inaccordance herewith and comprising an underlying polyurethane layerwould have a higher rated burst pressure than a polyurethane balloonformed from the same precursor. In addition, for some non-compliantcomposite balloon embodiments in accordance herewith, the rated burstpressure can be 10 bar, 15 bar, 20 bar, 25 bar, 30 bar, 35 bar, 40 bar,45 bar, 50 bar, 55 bar, 60 bar or more for a 4 to 8 mm in nominaldiameter medical balloon.

In accordance with another aspect of the present disclosure, thecomposite balloon body can be formed in a patterned/relief mold tocreate an outer balloon surface with one or more recesses orprotrusions. With reference to FIGS. 3 a-3 b , an embodiment of medicalballoon 300 can comprise a balloon wall 310 defining a chamber andcomprising a layered material 6, and the outer surface of balloon wall310 can define one or more recesses 312 or protrusions 314. Inparticular, layered material 6 comprises polymeric layer 5 having aporous microstructure and defining at least one recessed region 312and/or at least one protruding region 314. A “recessed” region 312 canbe a region with a higher degree of collapsed pores in the porouspolymeric layer. A “protruding” region 314 can be a region adjacentrecess 312 and has a lower degree of collapsed pores, if any.

The depth of recess 312 (or at least the relative amount of compressionbetween recessed region 312 and non-recessed (or protruding) region 314can be measured by comparing the thicknesses between two adjacentregions 312, 314. In various embodiments, recessed region 312 has aporous polymeric layer thickness that is approximately 90% relative tothe porous polymeric layer thickness of the non-recessed region 314. Aslight recess 312 might be one that is between 80% to 90% relativethickness, whereas a deep recess can be between 10% to 30% relativethickness. The amount of compression can be to some extent selectivelyadjusted through a number of factors including the width of thepatterned mold recess features, the width of the non-recessed featuresof the mold, the depth of the mold recess features, the pressure andtemperature of the process, the ratio of protruding features to recessedfeatures, the surface area density of mold recess features, the z-axiscompressibility of the porous material, and the compliancy of thepreform material. By controlling the process and selecting certainmaterials, in various embodiments, a recess's 312 relative thickness canbe 10%, 20%, 25%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,or any value therebetween compared to a non-recessed or protrudingregion. Because a protruding region 314 is protruding due to itsproximity to recessed region 312, the degree of protrusion can becontrolled by the same factors.

In addition to varying the degree of recess or degree of protrusion, thepattern of recesses 312 or protrusions 314 can also be varied byselectively varying the pattern of the mold. FIG. 4 illustrates aschematic transverse cross-sectional portion of a patterned balloon mold400. Shown are the relief features of the inner surface which comprise arecess 408 and a protrusion 410. A recess pattern on the mold can be anyrandom or repeated pattern. In various embodiments, the pattern is alongitudinal or circumferential striped/striated pattern, a helicalpattern, a polka dot pattern, a sinusoidal or zig-zag pattern, or anycombination thereof. The pattern can be dictated by the application orcan impart some benefit to the application. For example, in someembodiments, the outer surface of the balloon can have a plurality oflongitudinal striations or grooves and the grooves may facilitatepleating and folding the balloon into a delivery configuration and/orre-pleating the balloon after deflation. In addition, in variousembodiments, the recess features within the mold can have chamfered orrounded corners to reduce the strain on the porous layer at theserecess/protrusion transition areas during formation.

Mold recess 408 will facilitate the formation of a protruding feature314 on the balloon by being appropriately sized in both width to allowthe porous polymer to extend into recess 408 and tailoring the extent ofwhich the underlying thermoplastic polymer extends into the recess.Moreover, the depth of recess 408 can be tailored to vary the height ordegree of compression of a protrusion. Through consideration andselection of a width and depth of a mold recess, a temperature andpressure of the blow molding process, and the balloon preformcompliancy, this result can be achieved and even tuned to obtain adesired relative thickness and degree of microstructure compression.

A region of balloon 300 with a higher surface area of recesses 312 thanprotrusions 314 will have lower compliance than a region with a highersurface area of protrusions 314 than recesses 312. Thus, tailoring theratio of recesses 312 and protrusions 314 by region on the balloon bodycan be a way to tune the inflation profile of the balloon. For example,if it is desired to have the end portions of balloon 300 reach nominaldiameter faster than the center, the end portions of balloon 300 can bea higher proportion of protrusions 314 to recesses 312 than the centralportion of balloon 300.

The pattern of the mold can be selectively varied to define thepercentage of the total balloon surface area that is a protrudingregion, or conversely, a recessed region. In some embodiments, theplurality of the protrusion can cover 1% to 90% of the total balloonsurface area. In particular embodiments, the percentage of surface areathat has a surface protrusion can be 1%, 10%, 20%, 30%, 40%, 50%, 60%,70%, 80%, 90%, 99% or any value or range therebetween.

The described medical balloons like the embodiments depicted in FIGS. 1and 3 can have any appropriate dimension and sized for the clinicalapplication. Typically, a medical balloon is generally cylindrical alongthe working length. As shown, balloon 100, 300 have two opposed legportions 104, 304 that are integrally connected to shoulder/taperedportions 106, 306. For the purposes of this disclosure, “working length”is defined as the length of the straight body section 106, 306 of aballoon 110, 310 which comprises the approximate length between theopposed shoulder/tapered portions 106, 306. Leg portions 104, 304,shoulder/tapered portions 106, 306 and straight body section 108, 308defines a balloon overall length. The working length of balloon 100, 300can be about 10 mm to about 150 mm or more. Similarly, the nominaldiameter of the balloon can be about 2 mm to about 30 mm or more. By wayof example, a balloon can have a 4 mm diameter and a 30 mm workinglength, or alternatively, an 8 mm diameter and about a 60 mm workinglength. Of course, the balloon of the present disclosure can beconstructed at any dimensions appropriate for the specific use.

Porous polymeric layer 5 can extend over the entirety of balloon 100,300 or only be located on a portion of the balloon 100, 300. Forexample, porous polymeric layer 5 can extend only on body 108, 308 ofballoon 100, 300 or can only be located over one or moreshoulder/tapered portions 106, 306. During the making of balloon 100,300, tubular polymer member 210 comprising a porous microstructure canbe appropriately sized and positioned to the desired location overthermoplastic preform (parison) 220 in order to tailor where porouspolymeric layer 5 is located on balloon 100, 300.

By way of example, with reference to FIG. 5 a , the balloon 500 inaccordance with the present disclosure can be coated with a therapeuticagent 560. In further embodiments, a retractable sheath (not shown) canbe located about the balloon 500 to prevent or minimize release of saidtherapeutic agent 560 until the balloon 500 is at the desired treatmentsite. In various embodiments, an open porous microstructure canfacilitate therapeutic agent loading, the retention of the therapeuticagent on the balloon during processing, and delivery of the therapeuticagent. Similarly, in a “patterned” balloon embodiment, the size andpattern of the recesses can also influence the amount of loading, theretention of therapeutic agent on the balloon during processing, and thedelivery of the therapeutic agent to the surrounding tissue uponinflation. In order to facilitate coating and adhesion of a therapeuticagent, the surface of the porous layer can be plasma treated.

A “therapeutic agent,” as used herein, is an agent that can induce abioactive response or be detectable by an analytical device. Such agentsinclude, but are not limited to, radiopaque compounds, cilostazol,everolimus, dicumarol, zotarolimus, carvedilol, anti-thrombotic agentssuch as heparin, heparin derivatives, urokinase, and dextrophenylalanineproline arginine chloromethylketone; anti-inflammatory agents such asdexamethasone, prednisolone, corticosterone, budesonide, estrogen,sulfasalazine and mesalamine, sirolimus and everolimus (and relatedanalogs), anti-neoplastic/anti-proliferative/anti-mitotic agents such asmajor taxane domain-binding drugs, such as paclitaxel and derivatives oranalogues thereof, epothilone, discodermolide, docetaxel, protein-boundpaclitaxel particles such as ABRAXANE® (ABRAXANE is a registeredtrademark of ABRAXIS BIOSCIENCE, LLC), paclitaxel complexed with anappropriate cyclodextrin (or cyclodextrin-like molecule or otherclathrate), rapamycin and derivatives or analogues thereof, rapamycin(or rapamycin analogs) complexed with an appropriate cyclodextrin (orcyclodextrin-like molecule or other clathrate); 17β-estradiol,17β-estradiol complexed with an appropriate cyclodextrin or otherclathrate; dicumarol, dicumarol complexed with an appropriatecyclodextrin or other clathrate; β-lapachone and analogues thereof,5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones,endostatin, angiostatin, angiopeptin, monoclonal antibodies capable ofblocking smooth muscle cell proliferation, and thymidine kinaseinhibitors; anesthetic agents such as lidocaine, bupivacaine andropivacaine; an RGD peptide-containing compound, AZX100 (a cell peptidethat mimics HSP20; Capstone Therapeutics Corp., USA), hirudin,anti-thrombin compounds, platelet receptor antagonists, anti-thrombinantibodies, anti-platelet receptor antibodies, aspirin, prostaglandininhibitors, platelet inhibitors and tick antiplatelet peptides; vascularcell growth promoters such as growth factors, transcriptionalactivators, and translational promotors; vascular cell growth inhibitorssuch as growth factor inhibitors, growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bi-functional molecules consisting of a growth factor and acytotoxin, bi-functional molecules consisting of an antibody and acytotoxin; protein kinase and tyrosine kinase inhibitors (e.g.,tyrphostins, genistein, quinoxalines); prostacyclin analogs;cholesterol-lowering agents; angiopoietins; antimicrobial agents such astriclosan, cephalosporins, aminoglycosides and nitrofurantoin; cytotoxicagents, cytostatic agents and cell proliferation affectors; vasodilatingagents; agents that interfere with endogenous vasoactive mechanisms;inhibitors of leukocyte recruitment, such as monoclonal antibodies;cytokines; hormones or a combination thereof. In one embodiment, saidtherapeutic agent is a hydrophilic agent. In another embodiment, saidtherapeutic agent is a hydrophobic agent. In another embodiment, saidtherapeutic agent is paclitaxel.

In various embodiments, the coating on the balloon can comprise atherapeutic agent such as paclitaxel and at least one excipient. Suchexcipients can be a non-polymeric organic additive. For example, the (atleast one) organic additive can be independently selected from a listconsisting of 4-aminobenzoic acid, saccharin, ascorbic acid, methylparaben, caffeine, calcium salicylate, pentetic acid, creatinine,ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinicacid, glutaric acid, adipic acid, theophylline, and saccharin sodium.More particularly, the (at least one) organic additive can beindependently selected from the list consisting of 4-aminobenzoic acid,methyl paraben, caffeine, calcium salicylate and succinic acid. In oneembodiment the organic additive is succinic acid. In another embodiment,the organic additive is caffeine.

By way of second example, with reference to FIG. 5 b , balloon 500 inaccordance with the present disclosure can comprise medical device 570disposed about balloon 500. Balloon 500 can be used to expand medicaldevice 570 or touch up a medical device previously deployed orimplanted. As shown, medical device 570 is a stent, and moreparticularly a segmented stent, e.g., a stent comprising a plurality ofdiscrete annular stent members. As previously mentioned, the stent canbe balloon expandable or self-expanding.

A method of making a medical balloon in accordance with the presentdisclosure can comprise wrapping a film about a mandrelcircumferentially or helically to form a tubular precursor. The wrappedfilm can be bonded, such as through a heat treatment, and then removedas a tubular precursor from said mandrel. The tubular precursor can thenbe placed around a balloon preform (parison) and placed into a mold toundergo a stretch blow molding process. In an alternative embodiment,the tubular precursor can be placed around a fully formed balloon bodyand placed into a mold to undergo heating and pressurization.

The described medical balloons like the embodiments depicted in FIGS. 1and 3 can be used for a number of applications traditionally performedby other compliant, semi-compliant, or non-compliant balloons. Suchballoons can be used to perform a PTA procedure, deploy or seat amedical device, deliver a therapeutic agent, deliver RF energy, and/orin any other procedure that would benefit from its properties. When usedto deploy, seat, touch-up, or otherwise position medical devices, thedescribed balloon can be used in conjunction with any such devices, suchas balloon expandable or self-expanding stents or stent grafts, or otherendoluminal devices. In another embodiment, said composite balloon isconfigured to perform Percutaneous Transluminal Coronary Angioplasty(PTCA). In another embodiment, said composite balloon is configured totreat a coronary stenosis or obstruction. In another embodiment, saidcomposite balloon is configured to treat a peripheral artery stenosis orobstruction.

The balloon of the present disclosure may be employed in any bodyconduit, cavity, or vessel, including arteries and veins. The balloonembodiments can be used in a variety of medical balloon applications,such as a delivery device for a therapeutic agent to a surroundingtissue or for dilation of vessel, expansion of a stent, and/ortouching-up of a previously deployed stent or implanted vascular graft.A body conduit or cavity can include the urinary tract, the intestinaltract, nasal or sinus cavities, neural sheaths, intervertebral regions,bone cavities, the esophagus, intrauterine spaces, pancreatic and bileducts, rectum, and those previously intervened body spaces that haveimplanted vascular grafts, stents, prosthesis, or other type of medicalimplants.

A method of using a medical balloon in accordance with the presentdisclosure can comprise placing a composite balloon as described hereinin a vessel. Once in position, the balloon can be inflated to at least 4bar, at least 8 bar, at least 12 bar, at least 16 bar, at least 20 bar,at least 25 bar, at least 30 bar, at least 35 bar, or more, or any rangeor value therebetween.

Having generally described this disclosure, a further understanding canbe obtained by reference to certain specific examples illustrated belowwhich are provided for purposes of illustration only and are notintended to be all inclusive or limiting unless otherwise specified.

Testing Methods

It should be understood that although certain methods and equipment aredescribed below, any method or equipment determined suitable by one ofordinary skill in the art may be alternatively utilized.

Mass, Thickness, and Mass Per Unit Area

Membrane samples were die cut to form rectangular sections about 2.54 cmby about 15.24 cm to measure the weight (using a Mettler-Toledoanalytical balance model AG204) and thickness (using a snapgauge-Mutitoyo Model, 547-400, 0.5″ diameter foot). Using these data,mass per unit area was calculated with the following formula: m/(w*l),in which: mass per unit area (g/cm²), m=mass (g), w=width (cm), andl=length (cm). The average of three measurements was reported.

Bubble Point Test

The isopropyl alcohol bubble point was measured in the following manner:The material was restrained with a circular fixture of 1 inch diameter.The material was subjected to pressurized air at a pressurization rateof about 0.2 psi/sec. The pressure was increased until a stream ofbubbles appeared, followed by additional streams of bubbles at similarpressures. The reported values represent the average measurements forfive samples.

Matrix Tensile Strength (MTS) of Membranes

Tensile break load was measured using an INSTRON Model 1505 tensiletester equipped with flat-faced grips and a 0.445 kN load cell. Thesample dimensions were about 1 inch wide with about 2 inch gauge lengthtested at about 16.5% per second. For highest strength measurements, thelonger dimension of the sample was oriented in the highest strengthdirection. For the orthogonal MTS measurements, the larger dimension ofthe sample was oriented perpendicular to the highest strength direction.Each sample was weighed using a Mettler Toledo Scale Model AG204, thenthe thickness was measured using the snap gauge; alternatively, anysuitable means for measuring thickness may be used. The samples can thenbe tested individually on the tensile tester. Three different sectionsof each sample were measured. The average of the three maximum loads(i.e., peak force) measurements was reported. The longitudinal andtransverse matrix tensile strengths (MTS) were calculated using thefollowing equation: MTS=(maximum load/cross-section area)*(bulk densityof PTFE)/(density of the porous membrane), where an example of the bulkdensity of the PTFE was about 2.2 g/cm³.

Balloon Layer Adhesion Test or “157.5 Degree Peel Test”

The degree of adhesion was quantified in a “Peel Test.” This test wasperformed on an IMASS SP-2100 Slip/Peel Tester wherein the forcerequired to peel apart the layers of the composite 157.50° was measured.

To obtain the test sample, a sheet of layered composite material formedfrom the composite balloon, the balloon was transversely cut to removethe shoulders and then axially cut along the working length to form agenerally rectangular piece of material. Scotch tape was applied aroundthe ends of the sample on the porous layer side, with about 5 mm beingcovered by the tape and the remainder extending from the edge.

A 6 cm piece of double sided tape was adhered to the center of an IMASSSpecimen Test Panel, generally parallel to the long edge. The sheet ofmaterial, porous layer side-up, was adhered to the Test Panel with thedouble-sided tape at the center of the sample. The tape and porous layerfrom the underlying thermoplastic layer was placed on one end of thesample and the tape was folded over the edge to create a reinforced areato clamp into the IMASS.

A calibrated 5 lb load cell was used on the IMASS, and an adjustment ofthe transducer gripper was at a 115° angle to the front of the IMASS anda Variable Angle Peel Fixture was installed on to the platen. The testparameters are shown in Table 1. The gripper was positioned and thepeeled end secured into the gripper. The sample was peeled such that thesample is extending directly from the gripper in the straight line tothe specimen plate forming a 157.5° peel.

TABLE 1 IMASS Test Settings: Initial Platen Stop Force Speed Test DelayAveraging Mode unit unit Speed 0.1 10 seconds Test Time N mm/sec 1.0seconds mm/sec

Example 1—Precursor Porous Material

An expanded PTFE membrane that was amorphously locked and generally madein accordance with U.S. Pat. No. 3,953,566 had the following properties:thickness of approximately 25 μm, mass per area of approximately 9 g/m²,and a bubble point of approximately 14 kPa. This precursor material hada node and fibril microstructure shown in FIGS. 6 a (side 1) and 6 b(side 2).

Example 2—Precursor Porous Material

An expanded PTFE membrane that was amorphously locked and generally madein accordance with U.S. Pat. No. 7,521,010 had the following properties:thickness of approximately 5 μm, mass per area of approximately 11 g/m²,matrix tensile strength in the strongest direction of approximately 600MPa, matrix tensile strength in the direction orthogonal to thestrongest direction of approximately 230 MPa, strain in maximum load inthe strongest direction of approximately 19%, and strain at the maximumload in the transverse direction of approximately 160%. This precursormaterial had a microstructure shown in FIG. 6 c.

For forming circumferentially wrapped tubular members, in someembodiments, the precursor material was cut into a wide sheet or tape,wherein the strongest direction was transverse to the length of the tapeand the strongest direction was oriented axially in the formed balloon.In other circumferentially wrapped embodiments, the strongest directionwas along the length of the sheet or tape such that the strongestdirection was oriented circumferentially in the formed balloon. Forforming helically wrapped tubular members, the precursor material wascut into a tape, wherein the strongest direction was along the length ofthe tape.

Example 3—Construction of a Medical Balloon Comprising a NominalDiameter of 5 mm with a Smooth Surfaced Mold in Accordance with thePresent Disclosure

Step 3A: Tubular precursors were formed as follows: The precursormaterial from Example 1 and Example 2 having a 25 cm width wascircumferentially wrapped about a 0.133″ mandrel to form 5 layers (or 53mm of wrapped length). The precursor material was oriented on themandrel such that the strongest direction was along the length of thetube. This tubular precursor was then thermally treated in an oven at380° C. for 6 minutes with a protective overwrap and then removed fromthe oven. Once cooled, the protective overwrap was removed and thetubular precursor was removed from the mandrel.

Step 3B: A nylon balloon extrusion (Grilamid L25 balloon extrusion0.102″×0.068″) was preconditioned in an Interface Catheter Solutions CPS1000 parison stretcher to form the nylon preform according to theparameters in Table 2.

TABLE 2 Preform Parameters 10 × 62 Nylon 12 Heat - 330º F Run Cycle LeftSetup Right 120 Speed mm/s 120 130 Distance mm 130  7 Heat Time  7.7 sec 5. Dwell Time  5.5 sec Unheated Length 60.0 mm

Step 3C: Two balloon types were made with the tubular precursor preparedin Step 3A. A tubular precursor was slid over the balloon preformprepared in Step 3B and placed into a mold held by an Interface CatheterSolutions Balloon Forming Machine BFM 3310, ensuring both edges of ePTFEwere visible from the edge of the end plugs and were not connected tothe collet or clamp.

The stretch blow molding programs were run according to the followingtime, temperature, and pressure parameters of the heat-setting step. Aballoon made with the material described in Example 3 exhibitedparticularly good adhesion.

Time:

-   -   20 Seconds    -   45 Seconds    -   70 Seconds

Temperature:

-   -   285° F.    -   325° F.    -   350° F.

Pressure:

-   -   15 Bar    -   25 Bar    -   35 Bar

Step 3D: In some instances, the balloon body was placed upon a catheterand ends of the balloon body were secured to the catheter using astandard balloon catheter thermal bonding technique.

Example 4—Construction of a Medical Balloon Comprising a NominalDiameter of 5 mm with a Patterned Mold in Accordance with the PresentDisclosure

Composite balloons with the tubular precursor of Example 1 were preparedin accordance with Example 3. The mold was a 5×40 mm mold with thegeneral shape depicted in FIG. 2 with longitudinally oriented splinesmuch like that shown and described in FIG. 4 . The heat-setting step wasconducted at 285° F. for 45 seconds at 25 bar. FIG. 8 a is an SEM imageof the patterned balloon showing a recess region 312 and a porous region314 in the ePTFE microstructure. FIG. 8 b is an SEM image at a highermagnification showing the microstructure at a protruding region 312 and,conversely, FIG. 8 c is an SEM image at a higher magnification showingthe microstructure at a recessed region 314. By comparing the two, therelative amounts of collapse in the microstructure can be observed. FIG.8 d is an SEM image of the cross-section of the same patterned compositethat also shows the relative amounts of microstructure collapse, as aportion of a recess 312 is shown on the left-hand side of the image andthe protruding region 314 is central in the image.

Example 5—Construction of a Medical Balloon Comprising a NominalDiameter of 5 mm Using a Fully Formed Balloon Body

In an alternative embodiment, balloons were prepared in the method thatfollows: Composite balloons were prepared per Example 3 with asmooth-surfaced 5×40 mm standard mold with the shape depicted in FIG. 2and a heat-setting step conducted at 285° F. for 45 seconds at 25 bar,and others were prepared per Example 4 with a splined surface.

Step 5A: A tubular precursor was formed as follows: The precursormaterial from Example 1 and Example 2 having a 25 cm width wascircumferentially wrapped about a 0.133″ mandrel to form 5 layers (or 53mm of wrapped length). The precursor material was oriented on themandrel such that the strongest direction was along the length of thetube. This tubular precursor was then thermally treated in an oven at380° C. for 6 minutes with a protective overwrap and then removed fromthe oven. Once cooled, the protective overwrap was removed and thetubular precursor was removed from the mandrel.

Step 5B: A nylon balloon extrusion (Grilamid L25 balloon extrusion0.102″×0.068″) was preconditioned in an Interface Catheter Solutions CPS1000 parison stretcher to form the nylon preform according to theparameters in Table 2.

TABLE 2 Preform Parameters 10 × 62 Nylon 12 Heat - 330º F Run Cycle LeftSetup Right 120 Speed mm/s 120 130 Distance mm 130  7 Heat Time  7.7 sec 5. Dwell Time  5.5 sec Unheated Length 60.0 mm

Step 5C: After formation of the balloon body by inflation, one end ofthe balloon was plugged with a rapid-set adhesive, such as a UV-cureadhesive. A standard compression fitting with an appropriately sizedluer fitting was attached to the opposite open end, allowing forpressurization of the balloon by a pressure source.

Step 5D: An instrument such as a one designed for pleating and foldingmedical balloons was used. For a 10×62 mm balloon, balloon pressure wasset to approximately 25 psi. Pleating and compression die temperaturewas set to 50° C.±5° C. Compression pressure was set at or above 100psi.

Step 5E: Subsequent to pleating and folding the balloon body, apolymeric layer comprising a porous microstructure, wherein the porouspolymeric layer is an outermost layer, was added as an outer layer overthe balloon body. After placement over the balloon body, the multi-layerconstruct was placed back into the balloon mold. The construct waspressurized and heated to the same or similar settings as the previouslydescribed heat set settings. The following is a non-limiting example inthe formation of a composite balloon body:

Time:

-   -   70 Seconds

Temperature:

-   -   285° F.    -   350° F.

Pressure:

-   -   35 Bar

Example 6—Peel Test Study

A 157.5° Peel Test on composite balloon embodiments was prepared inaccordance with Example 3 (except for Step 3D) using a 10×62 mm smoothsurfaced, standard mold with the shape depicted in FIG. 2 . For thisPeel Test Study, a 3×3×3 full factorial experiment with the Time,Temperature, and Pressure parameters listed above was conducted,creating 27 possible conditions (summarized in the table of FIG. 7 a )with two additional replicates per condition (three total samples percondition) for each balloon type.

Results of a Peel Test, namely, peak kinetic force and average kineticforce, are shown in the Tables in FIGS. 7 b (i) and 7 b(ii).

Example 7—Construction of Drug-Coated Composite Balloons in Accordancewith the Present Disclosure

Composite balloons were prepared per Example 3 with a smooth-surfaced5×40 mm standard mold with the shape depicted in FIG. 2 and aheat-setting step conducted at 285° F. for 45 seconds at 25 bar, andothers were prepared per Example 4 with a splined surface. For someballoon samples, the outer balloon surface was further modified to havea plasma treated surface prior to coating with a drug. The ePTFE surfaceof the balloons was treated with an atmospheric plasma (TristarIndustries) operating at 65% of maximum voltage and 15 SCFH argon flow.A polyethylene (PE) or PTFE packing sheath was placed over the coatedballoon segment prior to sterilization. The packing sheath's primarypurpose was to maintain the balloon segment at its first diameter. Allsamples underwent ethylene oxide sterilization.

The outer ePTFE surface of each balloon construct was coated with an80/20 (dry w/w) paclitaxel/succinic acid coating formulation.Specifically, the balloons were coated by pipetting a known volume ofcoating solution onto a device while rotating the device at its inflateddiameter (5 mm). As solvent from the coating began to evaporate, theballoon was deflated and refolded to its first, un-inflated diameter byapplying a slow rate of evacuation to allow the balloon to refold.Coated balloons were dried overnight at room temperature in their foldedstate. With the exception of the “smooth composite” balloons, the finaldrug loading on all devices was approximately 3 μg paclitaxel (Ptx) permm². Since the smooth composite balloons had a smoother, thinner ePTFElayer (i.e., reduced void space) than the wrapped or splined designs,these devices were coated with less drug dosing (2 μg Ptx per mm²).Thus, more mass of drug was loaded on the balloon construct with thepattern of recesses and protrusions.

The prepared coated balloons (smooth, splined, and wrapped) were alsoused in an in vivo test to determine the amount of drug that releasedfrom the balloon substrate and delivered to the target tissue upondeployment. Prior to performing the in vivo procedure, angiography ofeach indicated peripheral artery was performed to obtain diameter andlength measurements of the treatment site. Diameter measurements at theproximal, midpoint, and distal portions of the treatment site determinedthe balloon inflation pressure required for appropriate vesselover-sizing. After completion of angiographic sizing, each balloonsample was tracked to the respective target site and deployed according.After tracking to the treatment site, each device was inflated to therequired inflation pressure for 60 seconds and subsequently deflated andremoved. Post-deployment, the balloon portion of each spent device wascut from the delivery catheter and analyzed for remaining Ptx content.

The artery target sites were also analyzed to determine amount of Ptxdelivered to the tissue. For each treated artery, mean Ptx levels in theproximal, treated, and distal segments were calculated by averaging Ptxlevels in all tissue sections in the indicated segment.

Based on the analyzed results between the initial amount on the balloonand the amount delivered to the tissue, the efficiency of the dosage wasdetermined (i.e., the percentage of the dose on the balloon that wasabsorbed in the tissue). Surprisingly, it was observed that the smoothballoons (with a collapsed microstructure) were more efficient atdelivering a drug to the tissue than the wrapped or splined designed.Thus, the smooth surfaced balloons can facilitate lower balloon dosing.

Numerous characteristics and advantages have been set forth in thepreceding description, including various alternatives together withdetails of the structure and function of the devices and/or methods. Thedisclosure is intended as illustrative only and as such is not intendedto be exhaustive. For example, embodiments of the present disclosure aredescribed in the context of medical applications but can also be usefulin non-medical applications. It will be evident to those skilled in theart that various modifications may be made, especially in matters ofstructure, materials, elements, components, shape, size, and arrangementof parts including combinations within the principles of the invention,to the full extent indicated by the broad, general meaning of the termsin which the appended claims are expressed. To the extent that thesevarious modifications do not depart from the spirit and scope of theappended claims, they are intended to be encompassed therein.

1. A medical balloon comprising a balloon wall defining a chamber andcomprising a layered material, wherein the layered material comprises: afirst polymeric layer, and a second porous, polymeric layer defining aporous microstructure, wherein the first polymeric layer is mechanicallycoupled to the second porous, polymeric layer by conforming andinterlocking the first polymeric layer with the second porous, polymericlayer without an adhesive agent such that material of the firstpolymeric layer and the second porous, polymeric layer are in anoverlying and interlocking relationship to each other.
 2. The medicalballoon of claim 1, wherein the layered material defines at least onerecessed region on an outer surface of the second layer, and wherein theat least one recessed region comprises a region of more collapsed poresin the second layer relative to a non-recessed region.
 3. The medicalballoon of claim 1, wherein the second layer includes a fluoropolymermaterial.
 4. The medical balloon of claim 1, wherein the first polymericlayer includes at least one of a thermoplastic, an expandedfluoropolymer, and a polyamide.
 5. The medical balloon of claim 4,wherein the thermoplastic comprises a blow-moldable thermoplastic. 6.The medical balloon of claim 1, wherein a surface of the first polymericlayer conforms and interlocks with an opposing surface of the porousmicrostructure of the second porous, polymeric layer.
 7. The medicalballoon of claim 1, wherein an interface between the first polymericlayer and the second porous, polymeric layer are characterized by anabsence of an adhesive agent.
 8. The medical balloon of claim 1, whereinthe first polymeric layer and the second, porous polymeric layer aremechanically coupled in overlying and interlocking relationship byhaving been stretched and engaged with one another by a stretch blowmolding process.
 9. The medical balloon of claim 1, wherein the firstpolymeric layer is seamless.
 10. A medical balloon comprising a balloonwall defining a chamber and comprising a layered material, wherein thelayered material comprises: a first, seamless polymer layer mechanicallycoupled to a second seamless polymer layer without an adhesive agent,the second seamless polymer layer comprising a porous microstructure,wherein the first, seamless polymer layer conforms to and interlockswith the second seamless polymer layer, the second seamless polymerlayer being an outer layer such that the balloon wall is seamless, andwherein the first, seamless polymer layer and the second, seamlesspolymer layer in an overlying and interlocking relationship to eachother.
 11. The medical balloon of claim 10, wherein the layered materialdefines at least one recessed region on an outer surface of the secondlayer, and wherein the at least one recessed region comprises a regionof more collapsed pores in the second layer relative to a non-recessedregion.
 12. The medical balloon of claim 10, wherein the first, seamlesspolymer layer comprises at least one of a compliant, semi-compliant, ornon-compliant thermoplastic material.
 13. The medical balloon of claim12, wherein the thermoplastic material is blow moldable.
 14. The medicalballoon of claim 10, wherein the second layer is anisotropic orisotropic.
 15. The medical balloon of claim 10, wherein the first,seamless polymer layer and the second, seamless polymer layer aremechanically coupled in overlying and interlocking relationship byhaving been stretched and engaged with one another by a stretch blowmolding process.
 16. A medical balloon comprising a balloon walldefining a chamber and comprising a layered material wherein the layeredmaterial comprises: a first layer at least partially mechanicallyadhered to a second layer without adhesive agent, wherein the firstlayer is a thermoplastic polymer layer and the second layer is afluoropolymer layer comprising a porous microstructure, wherein thesecond layer is an outermost layer of the balloon wall, and wherein thefirst layer is mechanically adhered to the second layer by conformingand interlocking with the porous microstructure of the second layerduring a blow molding process at a temperature that is above the glasstransition temperature but below the melt temperature of the firstlayer.
 17. The medical balloon of claim 16, wherein the first layer is atube, the second layer is a tube, and the second layer iscircumferentially wrapped about the first layer.
 18. The medical balloonof claim 16, wherein the layered material defines at least one recessedregion on an outer surface of the second layer, and wherein the at leastone recessed region comprises a region of more collapsed pores in thesecond layer relative to a non-recessed region.
 19. The medical balloonof claim 16, wherein the first layer and the second layer are capable ofseparating with 1 N/m of average kinetic force in a 157 degree PeelTest.
 20. The medical balloon of claim 16, wherein the first layer andthe second layer are capable of separating with 3 N/m of average kineticforce in a 157 degree Peel Test.